This Section carries out both basic and clinical research on the biological role and mechanisms of action of peptide growth factors such as insulin-like growth factors-I and -II (IGFs-I and -II) in embryonic development and reproduction. These particular growth factors have critical roles in development as proven by the fact that targeted deletion of IGF-I or IGF-II gene expression results in dwarfism and infertility - although how IGF deletion causes these defects is not yet understood. Molecular, immunological and radioligand probes are used to analyze the cellular sites of synthesis and action of these growth factors during embryonic development as well as in different physiological and pathophysiological situations in which IGFs have key roles. This Section has made a number of important and novel discoveries in the past year. 1) The insulin receptor-related receptor (IRR) is a newly discovered member of the IGF receptor family whose ligand and biological role are still unknown. This lab has shown that during embryonic development, the IRR is exclusively and synchronously co-expressed with the high-affinity nerve growth factor (NGF) receptor, TRK, suggesting that these two receptors are physically or functionally linked in determining the survival of sensory and sympathetic neurons - and that the IRR ligand is likely to be a novel neurotrophin. 2) The section has provided the first evidence that IGFs-I and -II cross the blood brain barrier with potency at least ten-fold greater than insulin, suggesting that systemic IGF levels may play an important role in relaying information concerning peripheral metabolic-nutritional status to brain regulatory centers. 3) The group has shown that production of components of the high molecular weight IGF binding complex, which is responsible for maintaining stable IGF levels in the circulation - is segregated into distinct hepatic cellular compartments which are differentially regulated by growth hormone. 4) of great importance for women's reproductive health, we have found that IGF-I appears to stimulate endometrial growth in the follicular phase of the menstrual cycle, while IGF-II appears to trigger endometrial decidualization in the secretory phase. These findings have very significant clinical implications in terms of the potential utilization of IGFs to selectively stimulate anabolic processes in the nervous and reproductive systems.